The controversial laboratory tool known as CRISPR may have found a whole new world to conquer. Already the favored method of editing genes, CRISPR could soon become a low-cost diagnostic tool that could be used practically anywhere to determine if someone has an infectious disease such as Zika or dengue.
CRISPR — which stands for Clustered Regularly Interspaced Short Palindromic Repeats — is basically a bacterial immune system that uses “molecular scissors” to snip away genetic material from invasive viruses. Early in this decade, researchers figured out how to exploit the natural system to craft a relatively cheap, remarkably easy-to-use technology for editing genetic codes almost as readily as using a word processor to revise a paragraph.
On Thursday, Feng Zhang, one of the pioneers of CRISPR, and 18 colleagues published a paper in the journal Science showing how they had turned this system into an inexpensive, reliable diagnostic tool for detecting nucleic acids — molecules present in an organism's genetic code — from disease-causing pathogens. The new tool could be widely applied to detect not only viral and bacterial diseases but also potentially for finding cancer-causing mutations.
CRISPR has been a sensation in the world of molecular biology, but the powerful tool has incited fears that it could be misused. Ethicists earlier this year released a report saying it should be limited in humans to treating diseases or disabilities, and with special caution when genetic changes would involve eggs, sperm or embryos and potentially be inherited by future generations. But CRISPR is already widely used in laboratory studies and has shown great promise in revealing the genetic origins of diseases, including cancer. This new application would propel CRISPR into the much less controversial realm of point-of-care disease diagnosis.
The new study has a whiff of marketing about it: Zhang and his colleagues have named their new tool SHERLOCK — for Specific High Sensitivity Enzymatic Reporter UnLOCKing.
“Nature is really amazing. Over the course of billions of years, it's come up with all these very powerful enzyme systems, and by studying the basic biology of these systems, some of them will give rise to important applications — like genome editing, like diagnostics,” Zhang, of the Broad Institute of MIT and Harvard, told The Washington Post.
Co-author Jim Collins, also of the Broad Institute, said, “In this diagnostic application we are really harnessing the power and diversity of biology. … I view it as a potentially transformative diagnostic platform.”
In essence they have taken the virus-recognition properties of the bacterial CRISPR system and turned it into a technique for telling if someone's blood, urine, saliva or other bodily fluid contains genetic markers of a pathogen. The earlier gene-editing tool used a molecule called CRISPR Cas9, but this one uses another enzyme, characterized for the first time only a year ago, and now dubbed Cas13a.
They report that their technique is highly portable and could cost as little as 61 cents per test in the field. Such a process would be extremely useful in remote places without reliable electricity or easy access to a modern diagnostic laboratory.
“We showed that this system is very stable, so you can really put it on a piece of paper and it will survive. You don’t have to refrigerate it all the time,” Zhang said.
“My head is spinning a little bit because this looks very, very provocative. And exciting,” said William Schaffner, a professor of infectious diseases and preventive medicine at Vanderbilt University Medical Center, who was not involved in the new research. “If you had something that could be used as a screening test, very inexpensively and rapidly, that would be a huge advance, particularly if it could detect an array of infectious agents.”
Collins said the scientists behind SHERLOCK have filed for patents on the technology, and are discussing ways to move their new tool from the laboratory to the clinical arena.
Zhang is one of the key figures in the CRISPR patent fight between the Broad Institute and the University of California at Berkeley, the latter the homebase of CRISPR pioneer Jennifer Doudna. The patent board ruled in favor of Zhang and Broad earlier this year. Doudna and another researcher had published their CRISPR discoveries first, but Zhang took the technique another step, into cells with nuclei, and the patent board ruled that the second step was sufficiently different that both could be eligible for patent protection. On Thursday, Berkeley and other interested parties filed an appeal of that ruling.
Scott Weaver, an infectious disease researcher at the University of Texas Medical Branch at Galveston, who was not involved in the new research, said after reading the study, “It looks like one significant step on the pathway which is the Holy Grail, which is developing point-of-care, or bedside detection, which doesn’t require expensive equipment or even reliable power.”